Infecting the Infectious: Viruses vs. Bacteria

Ramisa Maliha
Sophomore
School of Life Sciences
Independent University, Bangladesh

December 23, 2017

To be fair, bacteria are mostly our friends. The human body holds about 100 trillion commensal bacteria, that is, bacteria that do not harm us, and often benefit us. We can therefore think of them as part of our team. But not all bacteria are team players, as we are all very well aware. Disease-causing or pathogenic bacteria look to harm us in various ways, and many have even become resistant to multiple antibiotics, making treatment very difficult. But behold! Where there is life, there is predation. There is an entity on earth that outnumbers every living thing combined that most people are not even aware of: Bacteriophages (or phages, in short).

No, it’s not an insect nor some fantastic devourer of bacteria. These organisms, which are so simple that many do not label them as organisms at all, are even smaller than bacteria. Bacteriophages are viruses that infect bacteria. Bacteriophages that go through a certain kind of lifecycle end up rapidly killing the bacterial host. Because of their impressive action, bacteriophages have been employed as bacterial agents for 90 years to treat bacterial infections in humans and other species, and are prescribed to this day in places like Georgia and Russia. After all, the enemy of our enemy is our friend.

Phages on the surface of an Escherichia coli cell inject genetic material into the bacterium.© Eye of Science/Science Source

Bacteriophages first attach themselves to the surface of bacterial cells, and insert their genetic material (which can be DNA or RNA) into the bacteria by a syringe-like mechanism. The viral shell remains outside the bacterium. The injected viral genetic material utilizes the bacterium's resources and produces viral enzymes, as well as more viral genetic material. With the new viral proteins and enzymes, many new phage particles are assembled inside the host bacterium. Eventually the bacterium bursts (lyses), releasing the phage particles to infect neighboring bacteria after destroying the original host. Bacteriophages tend to be very specific to different hosts via surface binding interactions. For instance, a phage that infects Vibrio cholerae (the causative agent of cholera) would not affect Mycobacterium tuberculosis (the causative agent of tuberculosis). This property greatly accentuated their potential for use against specific pathogenic bacteria.

Frederick Twort, a bacteriologist from England is thought to be the first to suggest that phages could be used for killing bacteria in 1915. Later, Felix d'Herelle, a microbiologist at the Institute Pasteur in Paris, anticipated the use of phages to treat bacterial infection in humans, that is, phage therapy. In 1919 the first recorded phage therapy occurred when d'Herelle prescribed a mixture of phages to a 12-year-old boy with severe dysentery. At that time human trials were not as strictly regulated as we see today and the only method of knowing any side effects was for d’Herelle and his team to ingest the concoction themselves before prescribing it! According to the records, the boy’s symptoms cleared up after a single dose and he fully recovered within a few days.

Most of the results of the early research for phages to treat bacterial infections were published in non-English journals, and thus did not greatly influence research and therapy in Western Europe and the U.S. Having said that, bacteriophages were sold as a form of medication to treat a range of bacterial infections by a pharmaceutical company in the U.S called Eli Lilly as early as the 1940s. It was meant for treatment of wounds and upper respiratory infections. At that time phage therapy was not prevalent and efficient as there were no proper storage and purification methods. Also, it was not known that bacteriophages were very specific to the bacteria they attack. On top of that, the dawn of antibiotics (which were much faster and better understood) swept people off their feet and phage therapy fell out of use in most places.

Bacteriophages, as a form of therapy, have pros and cons. Most traditionally used antibiotics are broad spectrum, so along with destroying the pathogenic species of bacteria, they also destroy many beneficial bacteria making up a person’s microbiome. On the other hand, bacteriophages are very specific, which is ideal for treatment. However, bacteria can become resistant to the virus too. This problem is tackled by using phage cocktails, which incorporate many different phages targeting the same bacteria, making it very difficult for the bacteria to evolve resistance.

In the 1980s, the growing threat of antibiotic-resistant bacterial strains lead to Western scientists “re-discovering” phage therapy as a potential alternative. In the 2000s, human experiments began again, and data from the first phase I clinical trial in the U.S. was published in 2009. It is hoped that phage therapy will be an approved therapeutic option for bacterial infections throughout the world in the near future. In 2006 the Food and Drug Administration allowed the use of bacteriophages that attack strains of Listeria as a food additive on ready-to-eat meat products. This contribution of bacteriophages in the food treatment sector could be a peek into the future; replacing antibiotics and bringing an end to antibiotic-resistant supervillain bacteria such as MRSA!

Ramisa is a freshly minted second-year Microbiology student. She writes:

Biology has been the most intriguing subject to me for as long as I can remember. After being introduced to Microbiology, I found my passion in learning all about microscopic life that we interact with every day. I hope to indulge my passion by getting into the field of research and contribute to knowledge about microbes.

Rise of the Other Kind(s): Part III

Maliha Tanjum Chowdhury

Freshman

School of Life Sciences

Independent University, Bangladesh

July 13th, 2017

This the concluding part of  a three-part series of articles that aim to introduce the study of evolution using microbes as model systems while focusing on a recent study on speciation in bacteriophages.

After looking at infectivity of the bacteria by the differently evolved bacteriophages, the next factor studied was the adsorption rate – how well the phages can bind to either receptor protein. Surely enough, every specialist bacteriophage that had evolved had a binding affinity greater than the original or ancestral bacteriophage to their preferred host. Additionally, the scientists have also inferred that the gains in adsorption rate for the preferred receptor were greater than the losses on the alternative.

Now, to dig even deeper, the researchers meticulously sequenced phage alleles and measured the differences in gene sequences. All the specialists were found to have mutations in the host recognition gene J (the gene that codes for the protein that is responsible for binding to the bacterial host) and all individual mutations were seen to be non-synonymous – that is, the mutations resulted in changes in protein structure (which can be expected to ultimately affect binding). Interestingly, regardless of evolving by allopatry or sympatry, specialists for either type of receptor showed stronger genetic relatedness between themselves than with specialists of the other type.

Finally, the scientists resorted to cross-checking their findings to verify that their inferences were indeed true. They created new bacteriophages by artificially constructing the mutated alleles of either specialist, the ancestor EvoC strain, and a hybrid with all the mutations from the specialists for both receptors. Reality met expectations as the mutations found in either evolved strain did prove to be responsible for their respective host specializations and the genetic configuration of the ancestral EvoC was indeed seen to be expressing the generalist trait. The hybrid-child, sadly, did not prove to be viable. These observations not only confirm the J allele mutations as the cause of diversification, but also show how species may begin to emerge through mutations that result in reproductively incompatibility, proven by the production of non-sustainable hybrid progeny.

While I know all you science-mad kids are getting totally dizzy and starry-eyed marveling this experiment’s successes, it is always sensible to remember that even the coolest experiments are, to some degree, chained down by assumptions and reality. For instance, in this study, even with the substantial dissimilarities between them, the specialists are still much more similar than the cut-off for different species, that is, less than 70% sequence similarity. Not ones to be disheartened, the scientists argued that they did indeed observe the trademark processes that lead to eventual speciation, but did not let it run long enough for actual, classifiable species to emerge. 

Aside from this, there also surfaced some confusion over the incidence of genetic reversion – did the EvoC phage simply “go back” to being its ancestor, the predominant LamB-specialist? In depth analysis, however, put this matter to rest as among the 12 sequenced alleles, only 1 was seen to have reverted at a single site of the 5 mutations that set EvoC apart from its earlier ancestor. The LamB specialist can thus be described as much an independently evolved phage as the OmpF specialist. Another experimental drawback was in that Lambda phages are not completely sexual; also, phages need only a few mutations in a single gene to become reproductively isolated. As a consequence, it’s logical to think that these conclusions may not apply to speciation that requires more genetic change.

Apart from the specific constraints of this particular experiment, there always remain some basic unanswered questions – how likely is this effect to be a noteworthy and widespread one in nature? What key factors are responsible in speeding up or slowing down speciation? And, most importantly, what parameters can be measured to directly test the limits of speciation? These will be important open questions in evolutionary for a long time.

It’s been a riveting journey observing how life-forms function in response to the winds of change over the course of this experiment. It is no doubt that we owe our heartfelt gratitude to these brilliant minds as they have been able to physically show us the baby steps of a transition as complex and mind-boggling as evolution. Sure, saying that, in 50 more years, we might be able to “see” the monstrous Triceratops transform into the ethereal, enchanting peacock (for example) is a stretch. But because of such breakthroughs occurring ever so often in this millennium of miracles, I dare to dream that we understand the process much more clearly.

Maliha is a weirdo who somehow believes she's from a different planet. But she likes Earth just fine, and is fascinated by the science and beauty of life and has made it her purpose to explore it. Besides this, her most burning desires include becoming a synthetic biologist/ genetic engineer and running away with a heavy metal band.

Rise of the Other Kind(s): Part II

Maliha Tanjum Chowdhury

Freshman

School of Life Sciences

Independent University, Bangladesh 

July 6th, 2017 

This is the second in a three-part series that will broadly introduce and describe the study of evolution using microbes as model systems, and specifically focus on a recent study on speciation.

Practically, the fastest shift from one type of organism to another that can be observed in a laboratory is that of asexual microbes, e.g. bacteria and viruses. It is needless to say that for uncomplicated, single-celled chaps like viruses, bacteria and the like, rapid transition through numerous generations in a couple of hours or less is a walk in the park. Recall that any sort of genetic variation is simply the outcome of random, independent mutations in nucleotide or gene sequences. The accumulation of major changes which can possibly be observed between consecutive generations is far more evident in the case of microbes, as the hereditary fate of a given microbe is often entirely wielded by a single strand of DNA or RNA. We can select for some of these changes by providing different selection pressures.

However, speciation, based on our textbook definition, requires the incidence of sexual reproduction for organisms to diverge into distinct species (for them to no longer be reproductively compatible). Therefore, it is harder to define species when it comes to asexual microbes. 

In a recent study exploring sympatric and allopatric speciation, bacteriophage (viruses that infect bacteria) lambda was chosen as the model system to study the processes, as it not only divides rapidly asexually, but also has an exceptional ability to recombine with phages that coinfect the same host, thereby creating progeny and exchanging genes sexually. This allowed the conclusion of the study to be at least partially relevant to sexually reproducing species. Now, even though the rates and mechanisms of speciation may seem to vary for viruses and multicellular organisms, some features are comparable. For instance, reproductive isolation and incompatibility, which are concepts we learnt about earlier, mean much the same for viruses. In this specific case, reproductive incompatibility refers to the inability to recombine with other viruses whose nucleotide composition has evolved to differ considerably. Hence, all things considered, this was a clever model to work with.

We’re now going to delve deep into the experiment itself, so hold on to your seats, because it’s going to get much more science-y from here onwards. The researchers basically tried to observe the two kinds of speciation, allopatric (due to geographical separation) and sympatric (within the same environment), respectively, in the bacteriophage populations. The lab-generated bacteriophage lambda strain EvoC was the focus of the study. Bacteriophages begin their replication cycles by binding to receptor proteins on the host cell, and injecting their genomes into the cell. Individual bacteriophages tend to be very specific to the type and structure of the receptor proteins they can bind to. This virus, however, was a “generalist”- a bacteriophage with the ability to bind to both the OmpF and LamB receptor-proteins on the bacterial surface of Escherichia Coli.  

For this study, two different hosts were utilized: an E. coli strain carrying the OmpF receptor, and an E. coli strain carrying the LamB receptor. A broad summary of the experimental results is as follows: the bacteriophages, when supplied with just one of the two hosts, specialized in binding to the available receptor on that host while steadily losing the ability to bind to the other (allopatry).  More excitingly, when propagated on equal amounts of both hosts (and therefore in the presence of both receptors) together, the bacteriophages still divided into two distinct lineages with different host preferences (sympatry). In the light of these findings, the results shine through as compelling evidence that for the advent of distinct species, both allopatry and sympatry could play significant roles.

I personally feel that this article would remain terribly incomplete without including a walk-through of the methods used. So, here they are as follows:

1. Twelve bacteriophage (EvoC) populations, initially exactly the same, were grown with either one or other type of host, that is, six populations were grown in OmpF-expressing bacteria and the other six were grown in the LamB-expressing ones.
2. The bacteriophage populations were systematically passaged through the host populations for 35 cycles of dilution (the experiment took roughly a month in real world time).
3. In 8-hour intervals, bacteriophages were collected and stored.
4.  A fresh cycle of viral reproduction was kicked off by the transfer of 1% of the phage into a brand new population of host bacteria the next day.
5. Six other bacteriophage (EvoC) populations, initially exactly the same, were exposed to a culture of both types of host populations present in equal amounts, i.e. both OmpF and Lamb-carrying bacteria.
6. Steps 2-4 were conducted for these as well.

Step 1 is the allopatric set-up, as the isolated flasks containing only kind of host receptor represent geographical separation and different conditions from viruses growing only with the other type of receptor. Step 5 describes the sympatric experimental set-up, as viruses are allowed to switch between both available hosts and this may allow recombination between viruses that co-infect a given bacteria at some point. Lastly, to ensure a higher chance of co-infection – and thus, recombination between viruses – a high virus to bacteria ratio was maintained in all experimental units.

 A typical plaque assay. ASM

The results, as I passingly mentioned above, were beyond satisfactory. The scientists made their primary inferences based on observing clear regions, or “holes”, in lawns of bacterial colonies grown on standard agar plates.  This experimental method is known as the plaque assay – where the term “plaque” refers to the “holes” caused by viral growth. The plaques represent the ability of the bacteriophage to bind to the bacterial receptor. If there are no plaques, there has been no binding or infection.

Considerable significant receptor specialization evolved in all 12 bacteriophage populations which were grown on single bacterial hosts, and this conclusion was drawn on observation that bacteriophages that produced plaques on OmpF-expressing bacteria failed to do so on LamB-expressing ones, and vice versa. Again, more surprisingly, this was seen to be true for bacteriophages that were grown with both kinds of hosts together.

Therefore, even when both receptors were available, bacteriophages tended to become specialized for one kind of host. How and why might that be the case? What do these results really say about speciation? Find out the in the concluding part of this series next week. 

To be continued

Maliha is a weirdo who somehow believes she's from a different planet. But she likes Earth just fine, and is fascinated by the science and beauty of life and has made it her purpose to explore it. Besides this, her most burning desires include becoming a synthetic biologist/ genetic engineer and running away with a heavy metal band.

Rise of the Other Kind(s): Part I

Maliha Tanjum Chowdhury

Freshman

School of Life Sciences

Independent University

July 1st, 2017

This is the first in a three-part series that will broadly introduce and describe the study of evolution using microbes as model systems, and specifically focus on a recent study on speciation.

If you’re still one of those people who constantly pick their brains trying to figure out how a small, often seemingly benign creature like the bird could possibly be descended from the titan-like dinosaurs who once ruled the planet, you are not alone. The word evolution is generously and rightly paraded around to explain this phenomenon, but it is difficult for most to visualize. However, speciation, a word – an idea – much less known to the general public, comes much closer to explaining such transitions. Speciation describes the complex and extremely slow-paced chain of events that directly bring about this incredible metamorphosis from one creature to another over the course of millions of years.

Now, the term “species”, from which “speciation” has been derived, can be described as a group of organisms with strongly similar physical and biochemical properties. In more bookish terms, speciation is defined as the divergence of a single species into two (or more) groups of organisms so different from each other (and from the original species) that they can no longer produce viable, fertile young together. Allopatric speciation is when new species emerge due to a geographical rift between factions of the same population thereby exposing them to different selection pressures and thus, different responses to them. On the other hand, sympatric speciation is the emergence of divergent species from a single, original species in the same geographical region. The latter form of speciation is relatively harder to conceive as the incidence of reproductive isolation (wherein members of the same species stop interacting to reproduce) within closely knit communities is a much rarer phenomenon. However, this can be explained by the fact that separation often occurs due to separation into different ecological niches. For instance, individuals of an aquatic species may prefer to live near the surface or at the bottom of a pond, thereby leading to separation into different niches or locales within the same broad geographical location.

It is quite difficult to imagine how small changes in the characteristics of living organisms in response to different selection pressures could lead to the vast amount of biodiversity we see on earth. But a few billion years on the course of speciation, and magic happens – ancient amoeba-like creepy crawlers may transform to graceful sea-creatures, simple algal ancestors may flourish into magnificent flowering plants, and according to some, the ancestors of the apes that you go visit at the zoo may even turn into a person. The odds are as endless as the universe itself, and so, evolution is a beautiful thing – something quite poetic. It has helped and will continue to help scientists trace back to the ancestors of organisms that exist now, thereby creating a bridge between the present and some long-forgotten, illusory time in the past, and just simply help understand the dynamics of the living world better. Just as boundless oceans are formed from the assemblage of billions of droplets, a steady accumulation of mutations, products of recombination and the like generate more and more diversity and the uninterrupted influence of natural selection continually increases the frequency of fitter variants among this generated diversity. At the current moment, we see a snapshot of life on earth that is very far along, according to our sense of time. We see millions of different species that have evolved from a focal common ancestor.

Honestly, who wouldn’t want to play god and observe such enchanting changes under the microscope in their own little petri-dish? Sadly, and quite obviously, speed-racing through billions of years in a lab is NOT feasible, and thus we cannot hope to observe processes like the evolution of humans and birds. It is this powerlessness of humankind that has driven evolutional theorists and biologists to more often try and establish links between larger, multicellular species based on fossils, geological evidence, DNA sequences (when available), and mathematical modeling.

However, there does happen to exist a way of observing evolution in the lab, by using organisms that go through generations much, much faster than us...

To be continued

Maliha is a weirdo who somehow believes she's from a different planet. But she likes Earth just fine, and is fascinated by the science and beauty of life and has made it her purpose to explore it. Besides this, her most burning desires include becoming a synthetic biologist/ genetic engineer and running away with a heavy metal band.

Demystifying the Common Cold

Tahsin Tabassum

Sophomore

School of Life Sciences

Independent University, Bangladesh

June 1st, 2017

The common cold needs no introduction. We are all intimately acquainted with its symptoms and spread. But for a disease that occurs at an average of two to three times in adults and six times in children every year, its exact causes are not particularly well understood by the general population, and to a lesser extent, even by scientists. Broadly speaking, it is a viral infection that can be caused by more than 200 different types of viruses. The viruses mostly infect the upper respiratory tract including the throat and nose. The most common types of cold viruses that infect the body are rhinoviruses, corona viruses, respiratory syncytial virus (RSV) and parainfluenza virus. Rhinoviruses, the most common causative agents, cause up to 40% of all cases, and tend to be active during early autumn, spring and summer. Unknown viruses cause 20-30% of the infections, which is an endless source of consternation for scientists trying to develop vaccines against the disease.

A cold begins when viruses attach to cells in the lining of the nose and upper respiratory tract. Upon infection, the immune system (the body’s defense mechanism against germs) sends immune cells to attack these foreign cells. The immune cells release chemicals called cytokines in response to the infection. One of these cytokines, IL-6, is responsible for raising the body temperature, alongside causing inflammation. A raised temperature reduces the ability of the pathogens to reproduce effectively and cause damage. Meanwhile, the body overproduces mucus in the airways. Mucus is a sticky substance that lines the respiratory tract in order to trap dust and microbes that we breathe in with air. Beating cells called cilia constantly move mucus that has trapped particles up the respiratory tract; we subsequently swallow the mucus, and the viruses are destroyed by the acid present in our stomachs. Overproduction of mucus occurs as a result of the body trying to clear the virus. Symptoms of the disease are thus often caused by the body’s response against the cold virus. The virus takes advantage of many such symptoms, such as sneezing and cough, to spread to other individuals.

A poster from Great Britain during the Second World War. © IWM (Art.IWM PST 14140)

Symptoms vary in range and severity among individuals, but generally begin to disappear around a week after infection. The frequency of the disease decreases with age as children build up immunity or protection against many of the viruses they have already been infected by. It is easy to be dismissive of this relatively mild disease, but the common cold has significant economic costs through its effects on productivity in the workforce. How many sick days have you taken after you have come down with a bad cold?

Despite being such a commonly experienced ailment, various myths and misunderstandings persist about the common cold. Contrary to popular belief, being wet for too long or consuming cold things such as ice-cream in cold climates do not cause infection on their own. People also tend to often avoid dairy products when they have a cold because of the prevalent myth that these products increase mucus production. This is not true, and dairy products are actually recommended to help soothe sore throat. Symptoms of the common cold are also often confused with other conditions such as the flu as well as certain allergies as they have some similar symptoms such as runny nose and sore throat. However, it is important to distinguish between them in order to be able to decide on the course of treatment. The flu is caused by the influenza virus, for which specific drugs exist, while allergies occur as a result of an unregulated immune response to otherwise harmless substances found in our food and the environment, and are treated very differently from viral infections.

As for the common cold, there are no specific prevention or cure strategies. As a large number of different viruses are responsible for the common cold, it has not been possible so far to create a vaccine to protect against it, although a few are in the process of being developed. When infected, alongside the commonly observed strategies of rest, regular fluid intake to thin out the mucus, and taking decongestants to relieve nasal congestion and other symptomatic treatments, one should also take care to minimize contact with other individuals in order to limit spread.  If around infected individuals, maintaining good personal hygiene and wearing a face mask can go a long way to reduce risk of infection. 

Tahsin is a scientist-to-be with incredibly insane ideas and a soul full of ambitious dreams.

How to Not Get Away with Murder

Iffat Ara Sharmeen

Senior

School of Life Sciences

Independent University, Bangladesh

April 4th, 2017

The Timeline

In 1998, Dr. Richard Schmidt, a physician from Lafayette, Louisiana was proven guilty of second-degree attempted murder. He was sentenced to 50 years in prison. 

In 1984, Dr. Richard Schmidt began an extramarital affair with a married nurse called Janice Trahan that lasted 10 years. In 1994, Trahan divorced her husband, and then ended the relationship with Schmidt when he did not divorce his wife. On the night of August 4th, 1994, the doctor went to her house and gave her a shot while she was almost asleep, saying that it was a “vitamin B12 injection” and immediately fled. The shot was very painful, more so than the previous vitamin shots she had received from him. On August 16th, unusual symptoms started occurring. A series of visits to different specialists and tests finally revealed on January 3rd, 1995, that she was HIV-positive and Hepatitis C-positive.

Rising Suspicions and Mounting Evidence

Trahan concluded that the injection she received six months ago had not been a vitamin shot, and accused Schmidt of injecting her with infected blood during his visit on August 4th. To rule out other possibilities, prosecution had all of Trahan’s former sexual partners (she had had 7 sexual partners including Schmidt and her ex-husband between 1984 and 1995) tested for HIV. All of them were found to be HIV-negative. Trahan had also been a regular blood donor. The last time she donated blood was April 1994, and this was tested to be HIV-negative. This meant that she was infected with HIV after this, possibly via that injection. Prosecution also discovered that the doctor had drawn blood from an HIV patient under his care on August 4th, and this blood draw was recorded differently from the standard procedure in the hospital records.

A Tool from Evolutionary Biology

Genes are instructional codes found inside all organisms that determine the physical and biochemical characteristics of an organism, and the genome of an organism is its complete set of genes. Mutations refer to any changes in a genetic sequence. HIV mutates or changes very rapidly, and the fittest variants are selected for, and constantly replace older variants. This property of HIV lent this investigation to a new approach of establishing transmission in forensic investigations [1]. Since HIV mutates so fast, it was hypothesized that the viral genomic sequences from the doctor’s patient and Trahan would be more closely related to each other than to HIV viral sequences found in the rest of the population (if the virus had been transmitted between them). The hypothesis was explored using phylogenetic analysis, a tool commonly used in evolutionary biology to establish relationships between different species. 

During phylogenetic analyses, physical traits or genetic sequences are compared to infer the evolutionary relationships between organisms. Based on the similarities and differences in these characteristics, an evolutionary tree is produced, with similar sequences assumed to originate from a common ancestral sequence. In this investigation, HIV genomic sequences were used to construct phylogenetic trees. If HIV genomic sequences in all HIV-positive individuals were the same, determining the relatedness between viruses from different individuals would be impossible. However, owing to its high mutation rate and the resulting diversity, it was possible to infer with high levels of confidence the relationships between HIV viruses found in different individuals, using various statistical and tree-building methods.

A simple phylogenetic tree (left) and an example (right). These trees were generated for viruses for these analyses. Open curriculum

The Analysis

Researchers set out to investigate whether the viral genomes isolated from Trahan and the HIV- positive patient were closely related. HIV viral sequences from 32 other HIV positive patients in the same local area were also included for comparison. The comparisons were carried out by the Baylor College of Medicine and University of Michigan simultaneously to reduce risk of misinterpretation from laboratory errors. The HIV genome contains, among other genes, the env gene and the pol gene. The env gene produces proteins expressed on the surface of the virus, while the pol gene produces reverse transcriptase, the enzyme that initiates viral replication in the host cell. The two sequences are known to have different rates of evolution, and were compared between the victim, patient, the 32 individuals, and additional HIV viral sequences from elsewhere found in medical and research databases.

Results

As hypothesized, the gene sequences of the HIV viruses isolated from the patient and Trahan were more similar to each other than to the rest of the sequences included in the investigation. Baylor College of Medicine identified up to 99.87% similarity between the patient’s and victim’s env gene sequences, while University of Michigan identified up to 99.36% similarity. When they did the analysis for the pol gene, it turned out that the victim’s pol sequences formed a subset within the patient’s pol sequences. HIV viruses are tremendously diverse even within the same host; the pol sequences from  Trahan had branched out from a subset of the pol sequences from the patient that had presumably been successfully transferred in the blood sample collected by the doctor.

AZT is a drug used to treat AIDS. Viral pol sequences from Trahan and the patient had similar mutations that provided resistance against AZT. None of the others included in the investigation had the same mutations for resistance, suggesting that these mutations had evolved once and been transmitted between the two individuals.

All of this was consistent with the charge that Dr. Schmidt had deliberately injected HIV-infected blood into Trahan in an attempt to murder her. The phylogenetic analysis was ultimately a major component of the set of evidence used to build the case against the doctor. It remains a striking reminder of how tools and knowledge built from basic science can find more immediate application in the real world.

Bibliography:

[1] M. L. Metzker, D. P. Mindell, X.-M. Liu, R. G. Ptak, R. A. Gibbs, and D. M. Hillis, “Molecular evidence of HIV-1 transmission in a criminal case,” Proc. Natl. Acad. Sci. U. S. A., vol. 99, no. 22, pp. 14292–14297, Oct. 2002.

 Sharmeen is a fourth-year Biochemistry student at IUB. She loves to explore the world through a scientific lens.

Why We Need to Get a Flu Shot Every Year

Waaiz Alam Saad
Freshman
School of Life Sciences
Independent University, Bangladesh

April 13th, 2017

Influenza, which is often referred to as the "flu", is a viral respiratory disease which can cause severe complications and can even lead to death. Every year the influenza outbreak can seriously affect the population. The threat is especially high for children younger than 2 years, adults aged 50 years or older, pregnant women and also people with medical conditions.  The virus has the ability to spread rapidly between workplaces, homes, businesses and schools. Infection can result from inhalation of infected air, direct contact or by coming in contact with contaminated objects.

According to WHO, influenza occurs globally with an annual strike rate estimated at 5%-10% in adults and 20%-30% in children. Therefore, the best method to reduce chances of getting infected is to get vaccinated annually. The vaccine is a biological preparation which contains a dead or weakened strain of a pathogen or its toxin. The body produces defensive proteins called antibodies, which recognize and kill pathogens based on antigens (unique proteins or other molecules) found on or within the pathogen. The body retains memory of the pathogen, and is able to produce antibodies against the actual live pathogen if or when it is encountered.

Mortality from seasonal influenza and pneumonia, a common secondary infection from the flu, 2010-14. CDC

Each year, new vaccines need to be developed for influenza because these viruses are continuously changing and evolving. There are proteins on the surface of the virus called hemagglutinin (HA) and neuraminidase (NA). Our immune system identifies these proteins that are on the viral surface, and generates and produces antibodies against these proteins. The structures of the viral proteins are determined by genes. The genetic code of influenza changes or mutates frequently as it is very prone to copying errors when the viruses reproduce. If, for instance, there is a change in the gene encoding the HA protein, HA might change shape, and then antibodies that normally bind to the previous version of HA will no longer be able to. This would allow the newly mutated virus to evade the immune system. Mistakes or mutations occur randomly, so these changes occur slowly over time in a process known as antigenic drift. The consequence of this is that the virus eventually evolves resistance to any antibody that is common in a population.

Finding the ideal vaccine formula is therefore difficult. Vaccines are developed after careful surveillance and prediction of which strains will be common, and be likely to have an adverse impact, in the next year. Since the virus mutates rapidly, the effectiveness of vaccines can vary; they have been shown to decrease the danger of flu by about 50% to 60% among the overall population during times when most current flu viruses are same as the vaccine viruses. That may not seem like a lot, but if large percentage of the general population is protected by the vaccine, vulnerable individuals are less likely to come into intact with infected individuals. Vaccination therefore protects not only the vaccinated individual, but also others in the population; this is known as herd immunity. This is especially important for individuals who are at higher risk of acquiring severe flu, such as children, the aged, and people with certain chronic health conditions.

Saad is a Freshman at the School of Life Sciences. He plans to work in drug and vaccine development, and towards the improvement of diagnostic tools for infectious diseases.

What Is Dengue Anyway?

Samara Tawziat Choudhury
Sophomore
School of Life Sciences
Independent University, Bangladesh

March 30th, 2017

Every year from the month of July to October my mother goes berserk. She forces me to drink milk and eat eggs and vegetables every day. Now, you may ask - what could possibly push a mother to force feed her 20-year-old? The answer, for reasons I will explain, is dengue. In Bangladesh, at least 700 people are affected by dengue each year. We all have a general idea of what dengue is. A type of severe fever caused by mosquitoes that can, in many cases, lead to death. Well, today I would like to talk about all things dengue.

First and foremost, let us clarify something. It’s not the mosquito that causes the disease. It just acts as a vector, or in simpler words, carries the disease from one individual to another. What causes the disease is a virus known as dengue. Most of us have heard about viruses. But how many of us actually know what a virus is? A virus is a microorganism. Don’t get scared reading the name. It only sounds hard. Its meaning is actually pretty straightforward. “Micro” because it is so small we couldn’t possibly see it without a microscope. And “organism” because even though it is way too tiny for us to even imagine it, it is still very much a living thing.

Aedes aegypti after a blood meal. CDC

Now that we know what causes dengue, let us get back to the involvement of mosquitoes. It is actually a sort of a cycle. A mosquito bites a person infected with dengue and while sucking in the individual’s blood, the virus is also taken up by the mosquito. Many of us don’t know the mechanism of a mosquito bite. A mosquito actually pushes in two needle-like tubes into its victim’s blood vessels through their skin. One tube releases mosquito saliva that makes sure the blood does not clot, so that it can be quickly sucked in by the other tube. An infected mosquito can pass on the virus to a healthy individual through its saliva, and the virus replicates inside the individual. Then another mosquito may bite this person and thus, the cycle continues.

Not all mosquitoes cause dengue. The virus is primarily carried by mosquitoes of the Aedes aegypti species. It can be recognized by the black and white stripes throughout its surface. The symptoms of dengue include sudden, high fever, severe headaches, pain behind the eyes, severe joint and muscle pain, fatigue, nausea, vomiting and a skin rash, which appear two to five days after the onset of fever. In severe cases of dengue, especially with the onset of dengue hemorrhagic fever, the symptoms can also include bleeding or bruising under the skin, cold or clammy skin, nosebleeds, and large drops in blood pressure. This is where it gets serious, and without immediate medical attention, can be fatal.

Finally, I would like to go back to the months I mentioned in the beginning. Mosquitoes tend to lay their eggs in stagnant water because the eggs require water to hatch. In Bangladesh, the months from July to October are usually categorized as the rainy season. In these months, flooding may occur and drainage systems may get all clogged up, providing mosquitoes with the perfect breeding grounds to lay their eggs. Therefore, it is important that dirty water bodies are cleaned out regularly. Also, we should make it a habit to use mosquito repellents and mosquito nets to reduce chances of getting bitten by an infected mosquito. And, in the end, if you want to have a strong immune system to fight the dengue virus, it may not be a bad idea to take my mother’s number one advice- eat healthy as this would better prepare your body to fight infection in the event that it occurs.

Samara dreams of curing diseases and working for the WHO. She also loves to cook, and has a weird wish to be buried in a library so that her soul can read books for eternity.

How Smallpox Was Conquered

Farina Afrin Malik

Freshman

School of Life Sciences

Independent University, Bangladesh

March 23rd, 2017

From the day we are born and sometimes prior to birth, we humans have had one constant companion: disease. However for as long as disease has existed so has our ability to survive despite them. Over the centuries, by sheer perseverance humans have discovered many ways of treating these diseases. We have made great advancements in our methods of treatment and have attained means of curing and preventing innumerable diseases. One such illness that we have actually managed to successfully eradicate is smallpox.

Smallpox is known to be caused by a virulent form of the Variola virus. The symptoms of this disease include small rash-like bumps forming all over the body. Some may confuse smallpox to be chickenpox, as their symptoms are quite similar, but their most distinct difference would be the fatality rate. Smallpox had a 30% death rate, unlike chickenpox which has a less than 1% mortality rate. Smallpox also often resulted in lifelong scarring and disfiguration whereas chickenpox causes mild scarring which would heal with time. 

Public domain

An 18^th century English scientist, Edward Jenner, was the mastermind behind the vaccine; he discovered that milkmaids who were infected with a milder disease called cowpox (a viral disease which commonly occurs in cows) did not suffer from smallpox. He transferred some of the fluid found in the pustules in the skin from the cowpox-infected person to a healthy individual, and later challenged him with smallpox. The disease was effectively prevented, suggesting that exposure to cowpox had somehow made the individual immune to, or protected against smallpox. Edward Jenner coined the term vaccinia to denote cowpox, and this became the origin for the term vaccine.

Since Jenner lived in a time with much more lax ethical standards in society, he was able to carry out human testing. Today however, animal testing of some form is carried out before human trials since it is considered unethical and risky to test on humans first. 

Jenner's original discovery led to the development and standardization of a commercial vaccine against smallpox. To continue the work started by Jenner, many individuals all over the world collaborated to establish The Smallpox Eradication Programme that began its work in 1966. One of their main techniques that helped in conquering this disease was the “ring vaccination” method. This particular form of vaccination involved administering the vaccine to all the individuals living in a radius surrounding an infected person so that the disease would not spread beyond this area. Infected and exposed individuals were isolated or quarantined to minimize spread.

As part of the worldwide eradication effort, the exact same methods of treatment were conducted in Bangladesh during the 1970s, by the American doctor, D.A. Henderson who traveled across the country examining every case of smallpox and preventing it from being spread to neighboring villages. Once all individuals had been vaccinated, he offered rewards to anyone who could bring forth a patient who had acquired smallpox. Near the end of the decade, the disease was declared by the WHO (World Health Organization) to have been successfully eradicated. 

From this success we can gather that with large-scale collaborative effort, it may be possible to replicate this for other pathogens. It is also quite likely that it may happen sooner than we expect, as recent updates state that polio and measles are on the road to eradication as well.

Farina is a Freshman at IUB who aspires to be a biomedical scientist. In her free time, she enjoys delving into the sciences of baking and imaginative fiction.

Revisiting the 2009 Swine Flu Pandemic

Amira Mohammed Ali
Senior
School of Life Sciences
Independent University, Bangladesh

23rd March, 2017

Influenza, commonly known as the "flu", is a disease caused by the influenza virus. The virus is known for its ability to cause pandemics, in which cases of the disease spread across multiple continent. The 1918 Spanish flu pandemic is estimated to have killed up to 50 million people. The virus has resulted in a few more pandemics since then, notably the 1957 pandemic that claimed around 4 million lives worldwide, and most recently the 2009 swine flu pandemic. Influenza virus has several subtypes, and is known to frequently produce new strains. It not only also has the ability to adapt through mutations or random changes in its genetic code, but can also exchange genes with other strains of influenza in cases where two or more strains infect the same individual. Seasonal influenza is very common and occurs every winter throughout the globe, and the new strains we see every year occur mostly as a result of accumulating mutations. The other mechanism of variation, in which exchange of genes can create new, unpredictable strains, resulted in the 2009 H1N1 pandemic strain which had never infected humans before. It was derived from an animal influenza strain, and different from the seasonal H1N1 strains that normally affect humans.

The first infection with this new strain is believed to have occurred in March 2009 in Mexico. Immediately after the first case, suddenly a number of these new H1N1 infection cases were rushed into many clinics across the country. The outbreak received increasing attention as the infection started to spread out to the northern parts of America. The CDC (Center for Disease Control) collected patient samples from infected people, and confirmed the emergence of the new strain. After few weeks of initial emergence of the new virus, it spread to 74 countries causing 29000 cases. The WHO (World Health Organization) declared it a global pandemic. The number of infected patients increased steeply as the winter approached globally.

Intensity map of confirmed cases of 2009 swine-derived H1N1 influenza. Public domain

To tackle the infection, a huge number of antiviral drugs, Oseltamivir and Zanamivir, were released to treat the patients. When existing drug supplies were insufficient and sometimes ineffective in meeting the rapidly increasing demand for treatment, the FDA (Food and Drug Administration) issued emergency use of previously unapproved antivirals and diagnostic tests for the H1N1 strain. Other measures were taken at that time to halt the spread, e.g. by monitoring airports.

After these efforts, the pandemic started to decline from May 2010 and in August 2010, the WHO declared that it was over. Even though the pandemic was over, it had taken more than 18,000 lives (laboratory confirmed) and made many more people sick globally. The WHO then declared a post-pandemic period where people received help to overcome the difficulties they had gone through. To help prevent any such pandemic in the future, the US government and private manufacturers have developed a vaccine in the form of injections (flu shots) and nasal spray, for swine-derived H1N1 influenza virus.

Amira is a wanderer and tries to understand the wonders of life. She wishes to have a lab of her own one day where she will unravel the mystery of life.